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Purpose: To evaluate whether the etch-and-rinse or self-etching mode of a universal adhesive is the best protocol to optimize bond strength to primary and permanent artificially-induced caries-affected dentin. Materials and Methods: Flat midcoronal dentin surfaces were exposed in 24 primary and 24 permanent molars and submitted to pH cycling for 14 days to induce artificial caries-affected dentin. For each tooth type (primary and permanent), the teeth were randomly assigned to 4 different groups according to the adhesive systems and bonding strategy: a universal adhesive, Scotchbond Universal Adhesive, in self-etching and etch-and-rinse modes; a twostep etch-and-rinse adhesive, Adper Single Bond 2 (control); and two-step self-etching system, Clearfil SE Bond (control). After bonding and restorative procedures, specimens were sectioned to obtain rectangular sticks (0.8 mm2) that were submitted to microtensile tests (crosshead speed: 1 mm/min). The data were analyzed using two-way ANOVA (α = 0.05). Results: The universal adhesive showed bond strengths similar to those of the control groups, irrespective of the bonding strategy. Likewise, statistically similar bonding performance was observed for all adhesives to either artificially- induced caries-affected primary or permanent dentin. Conclusion: The new universal adhesive, Scotchbond Universal Adhesive, can be used in both application modes in artificially-induced caries-affected primary and permanent dentin, as the bond strength was not influenced by the different substrates or application mode.